Compact hydraulic manifold structure for shear sensitive fluids

ABSTRACT

An compact hydraulic manifold for transporting shear sensitive fluids is provided. A channel network can include a trunk and branch architecture coupled to a bifurcation architecture. Features such as tapered channel walls, curvatures and angles of channels, and zones of low fluid pressure can be used to reduce the size while maintaining wall shear rates within a narrow range. A hydraulic manifold can be coupled to a series of microfluidic layers to construct a compact microfluidic device.

BACKGROUND

The wall shear rate for blood travelling through a network of channelsmust be maintained within a limited range to preserve blood health.Shear rates outside of the acceptable range can lead to clotting orhemolysis. Blood health is important in organ assist devices, whichoften contain channels carry blood. Patient mobility can also be animportant factor in the success of an organ assist device. It istherefore desirable to have a compact channel network architecture thatis capable of safely transporting blood and other shear sensitivefluids.

SUMMARY OF THE INVENTION

Aspects and implementations of the present disclosure are directed to acompact hybrid hydraulic manifold structure for shear sensitive fluids.

At least one aspect is directed to a microfluidic device. Themicrofluidic device includes a first network of channels having aplurality of First Channels. Each First Channel has a height in therange of about 50 microns to about 500 microns, a width in the range ofabout 50 microns to about 1.5 millimeters, and a length in the range ofabout 3 centimeters to about 20 centimeters. The microfluidic deviceincludes a second network of channels having at least one Second Channelcomplementary to one or more of the First Channels. The microfluidicdevice includes a filtration membrane separating the one or more FirstChannels from the at least one Second Channel. The plurality of FirstChannels includes an input channel forming a primary channel, aplurality of secondary channels, and an outlet channel. A firstsecondary channel connects to the primary channel at a first junctionlocated at a first distance along the primary channel. A secondsecondary channel connects to the primary channel at a second junctionlocated at a second distance, greater than the first distance, along theprimary channel. The primary channel and the first and second secondarychannels are configured such that flow of fluid through the primarychannel beyond the first junction is substantially greater than flow offluid into the first secondary channel

In some implementations, the plurality of First Channels is locatedwithin a first substrate. The first substrate can have a thickness inthe range of about 10 microns to about 10 millimeters.

In some implementations, at least one of the first and second secondarychannels of the microfluidic device bifurcates into first and secondtertiary channels at a third junction, such that a fluid flow ratethrough the first tertiary channel is substantially the same as a fluidflow rate through the second tertiary channel, and the total fluid flowrate between the first and second tertiary channels is substantially thesame as the fluid flow rate through the portion of the at least onesecondary channel between the primary channel and the third junction.

In some implementations, the microfluidic device includes a flow dividerfor dividing fluid flow between the first and second tertiary channels.The flow divider has a curved surface connecting to the walls of thefirst and second tertiary channel, and the radius of curvature of theflow divider is not greater than the hydraulic diameter of the at leastone secondary channel. In some implementations, the microfluidic deviceincludes third and fourth tertiary channels that converge at a pointwhere they have opposing curvatures to form a third secondary channel,such that all of the fluid flowing through the third and fourth tertiarychannels is subsequently transported into the third secondary channel.

In some implementations, the diameter of at least one secondary channelat a portion adjacent to its junction with the primary channel issignificantly greater than the diameter of the downstream portion of theat least one secondary channel, such that a zone of low fluid pressureis created at the junction. In some implementations, an angle formed bya centerline of the secondary channel and a downstream portion of thecenterline of the primary channel measures in the range of about one toabout sixty degrees. In some implementations, the channels are furtherconfigured to maintain a shear rate of within a range of about twohundred inverse seconds to about two thousand inverse seconds when bloodis transported through the channels. In some implementations, the wallsof the primary channel are disposed at an angle of no greater thanthirty degrees with respect to the direction of fluid flow through theprimary channel.

In some implementations, at least one secondary channel includes acurved portion directing flow away from the primary channel. In someimplementations, the curved portion of the at least one secondarychannel has a radius of curvature that is not less than its hydraulicdiameter.

At least one aspect is directed to a microfluidic device. Themicrofluidic device includes a first manifold having a primary inletchannel and a plurality of secondary inlet channels, coupled to a firstplurality of substrates each having a network of First substratechannels. The microfluidic device includes a plurality of secondsubstrates. Each second substrate corresponds to one of the firstsubstrates and includes at least one Second channel complementary to oneor more of the First substrate channels. The microfluidic deviceincludes a plurality of filtration membranes. Each filtration membraneseparates the First Channels of one of the plurality of first substratesfrom the at least one Second channel included in a corresponding secondsubstrate. Each of the First substrate channels has a height in therange of about 50 microns to about 500 microns, a width in the range ofabout 50 microns to about 1.5 millimeters, and a length in the range ofabout 3 centimeters to about 20 centimeters. A first secondary inletchannel connects to the primary inlet channel at a first junctionlocated at a first distance along the primary inlet channel. A secondsecondary inlet channel connects to the primary inlet channel at asecond junction located at a second distance, greater than the firstdistance, along the primary inlet channel. The inlet channels areconfigured such that flow of fluid through the primary inlet channelbeyond the first junction is substantially greater than flow of fluidinto the first secondary inlet channel.

In some implementations, the network of First substrate channels in atleast one of the first plurality of substrates comprises a primarysubstrate channel and a plurality of secondary substrate channels. Themicrofluidic device includes a first secondary substrate channelconnecting to the primary substrate channel at a first junction locatedat a first distance along the primary substrate channel. Themicrofluidic device includes a second secondary substrate channelconnecting to the primary substrate channel at a second junction locatedat a second distance, greater than the first distance, along the primarysubstrate channel. The substrate channels in the microfluidic device areconfigured such that flow of fluid through the primary substrate channelbeyond the first junction is substantially greater than flow of fluidinto the first secondary substrate channel.

In some implementations, the microfluidic device includes a secondmanifold having a primary inlet channel and a plurality of secondaryinlet channels, coupled to a second plurality of substrates each havinga network of Second substrate channels. The microfluidic device includesa first secondary inlet channel connecting to the primary inlet channelat a first junction located at a first distance along the primary inletchannel. The microfluidic device includes a second secondary inletchannel connecting to the primary inlet channel at a second junctionlocated at a second distance, greater than the first distance, along theprimary inlet channel. The network of secondary channels of each of thesecond plurality of substrates connects to a secondary inlet channel ata junction such that fluid can be transported from the second manifoldto the network of Second substrate channels of each of the secondplurality of substrates.

In some implementations, each of the second plurality of substrates iscoupled to a respective one of the first plurality of substrates to forma bilayer. In some implementations, an angle formed by a surface of atleast one of the first plurality of substrates and the downstreamportion of the primary inlet of the first manifold is in the range ofabout one to about sixty degrees.

These and other aspects and implementations are discussed in detailbelow. The foregoing information and the following detailed descriptioninclude illustrative examples of various aspects and implementations,and provide an overview or framework for understanding the nature andcharacter of the claimed aspects and implementations. The drawingsprovide illustration and a further understanding of the various aspectsand implementations, and are incorporated in and constitute a part ofthis specification.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings are not intended to be drawn to scale. Likereference numbers and designations in the various drawings indicate likeelements. For purposes of clarity, not every component may be labeled inevery drawing.

FIG. 1A is a depiction of a first microfluidic device according to anillustrative implementation.

FIG. 1B is a depiction of a second microfluidic device according to anillustrative implementation.

FIG. 2 is a depiction of a single substrate layer that can be used inthe microfluidic device of FIG. 1A or FIG. 1B, according to anillustrative implementation.

FIG. 3 is a schematic view of a network of channels.

FIG. 4 is an enlargement of a portion of the network of channels shownin FIG. 3.

FIG. 5 is a schematic view of a network of channels.

FIG. 6 is a schematic view of a network of channels.

DESCRIPTION OF CERTAIN ILLUSTRATIVE IMPLEMENTATIONS

Following below are more detailed descriptions of various conceptsrelated to, and implementations of, a compact hydraulic manifoldstructure for shear sensitive fluids. The various concepts introducedabove and discussed in greater detail below may be implemented in any ofnumerous ways, as the described concepts are not limited to anyparticular manner of implementation. Examples of specificimplementations and applications are provided primarily for illustrativepurposes.

FIG. 1A depicts a microfluidic device 100 composed of eight bilayers, asexemplified by the bilayer 102. Each bilayer 102 consists of a bloodsubstrate layer, such as the blood substrate layer 104, and a filtratesubstrate layer, such as the filtrate substrate layer 106, separated bya permeable membrane, such as the permeable membrane 108. A network ofchannels within the blood substrate 104 and the filtrate substrate 106allows fluid (i.e. blood or filtrate) to be transported. Themicrofluidic device 100 also includes a blood inlet manifold 110 and ablood outlet manifold 112, both coupled to the blood substrate layer104. Similarly, a filtrate inlet manifold 114 and a filtrate outletmanifold 116 are coupled to the filtrate substrate layer 106. Bloodenters the blood substrate layer 104 through the blood inlet manifold110 and exits through the blood outlet manifold 112. Filtrate enters thefiltrate substrate layer 106 through the filtrate inlet manifold 114 andexits through the filtrate outlet manifold 116.

In one implementation, each bilayer 102 is parallel to each otherbilayer 102, as shown in FIG. 1A. Although FIG. 1A depicts the bilayers102 as perpendicular relative to the manifolds 110, 112, 114, and 116,this orientation is not essential. For example, FIG. 1B shows analternative arrangement, in which the blood inlet manifold 110 and theblood outlet manifold 112 are not perpendicular to the bilayers 102.This configuration reduces the angle through which the blood flows as itenters into the blood inlet manifold 110, flows through the bilayer 102,and exits through the blood outlet manifold 112. The blood substratelayer 104 and the filtrate substrate layer 106 each have a thickness inthe range of about 10 microns to about 10 millimeters, and the membrane108 has thickness in the range of about 500 nanometers to about 1millimeter. In some implementations, adjacent bilayers 102 can be incontact with one another. In other implementations, the bilayers 102 canbe separated by a distance of about 500 microns or more, as shown inFIG. 1.

The device 100 is designed for use in hemofiltration. The network ofchannels within the blood substrate layer 104 and the filtrate substratelayer 106 divide the fluid (i.e. blood and filtrate) so that arelatively large surface area of each fluid is exposed to the permeablemembrane 108. Each channel of the blood substrate layer 104 is alignedwith a corresponding channel of the filtrate substrate layer 106, sothat the corresponding channels are separated by the permeable membrane108. As the blood moves through the channels of the blood substratelayer 104, filtrate moves in the opposite direction through the filtratesubstrate layer 106 and waste products and water are removed from theblood via diffusion through the permeable membrane 108 into the filtratesubstrate layer 106. Healthy blood remains in the blood substrate layer104 and can then be recirculated into the body of a patient.

The blood inlet manifold 110 has a primary channel 118 coupled toseveral secondary channels, as exemplified by the secondary channel 120.The other manifolds 112, 114, and 116 have primary and secondarychannels similar to the primary channel 118 and secondary channel 120.Features of the blood manifolds 110 and 112, such as the curved shape ofthe channels, help to preserve blood health. These features aredescribed further below. The shape of the filtrate manifolds 114 and 116are less important, because filtrate is typically not a shear sensitivefluid like blood.

The blood substrate layer 104 and the filtrate substrate layer 106 canbe made of a thermoplastic, such as polystyrene, polycarbonate,polyimide, or cyclic olefin copolymer (COC), biodegradable polyesters,such as polycaprolactone (PCL), or soft elastomers such as polyglycerolsebacate (PGS). The substrate layers 104 and 106 may alternatively bemade of polydimethylsiloxane (PDMS), poly(N-isopropylacrylamide), ornanotubes or nanowires formed from, for example, carbon or zinc oxide.The substrates 104 and 106 are made of an insulating material tomaintain temperature stability. In some implementations, the channelscan be coated with cytophilic or cytophobic materials to promote orprevent the growth of cells, such as vascular endothelial cells, in thechannels. The channels may also be coated with an anticoagulant to helpprevent clotting of the blood in the blood substrate layer 104.

FIG. 2 illustrates a blood substrate layer 200 suitable for use as theblood substrate layer 104 of FIG. 1A. The blood substrate layer 200 hasa network of channels, which includes a primary channel 202, secondarychannels such as channel 204, tertiary channels such as channel 206,quaternary channels such as channel 208, and an outlet channel 210. Theblood substrate layer 200 has a thickness in the range of about 10microns to 10 millimeters. In some implementations, each channel has aheight in the range of about 10 microns to about 1 millimeter and awidth in the range of about 50 microns to about 1.5 millimeters. In someimplementations, the width of each channel is less than about 900microns.

As used herein, the term “height” refers to the greatest depth of eachchannel. The term “width” refers to the greatest distance betweeninterior edges of a channel, as measured in a direction perpendicular tothe flow of fluid and within the plane occupied by the substrate layercontaining the channel. In some implementations, each channel can have asubstantially semi-circular cross-section. In other implementations, thechannels may have rectangular or trapezoidal cross sections. In stillother implementations, the cross sections of the channels can beirregular in shape. For example, the channel may be generallyrectangular with rounded or faceted corners. Alternatively, the channelsmay have flat top and bottom walls joined by curved sidewalls. Eachchannel is created by etching, milling, stamping, plating, directmicromachining, or injection molding. The top portions of the channelson the blood substrate layer 200 are open and do not include a top wall.In the final configuration of the microfluidic device 100 shown in FIG.1A, the permeable membrane 108 will be placed in contact with the bloodsubstrate layer 200 to form enclosed channels.

The blood substrate layer 200 also includes alignment features 212 tofacilitate alignment of the blood substrate layer 200 with the permeablemembrane 108 and the filtrate substrate layer 106 of FIG. 1A to form abilayer, such as the bilayer 102. This can ensure the correctorientation of the blood substrate layer 200 with respect to thepermeable membrane 108 and the filtrate substrate layer 106.Characteristics of the network of channels in the blood substrate layerare further discussed below.

FIG. 3 depicts a network of channels 300. The network of channels 300includes a trunk channel 302, branch channels 304A-304C, and bifurcationchannels 310A-310F. In one implementation, portions of the network ofchannels 300 represent the network of channels within the bloodsubstrate layer 200 shown in FIG. 2. For example, the trunk 302 of FIG.3 can correspond to the primary channel 202 of FIG. 2, the branchchannel 304A can correspond to the secondary channel 204, thebifurcation channel 310A can correspond to the tertiary channel 206, andthe bifurcation channel 310C can correspond to the quaternary channel208. In another implementation, the network of channels 300 representsthe channels in the blood inlet manifold 110 and the blood outletmanifold 112 of FIG. 1A. For example, the trunk 302 can represent theprimary channel 118 and the branch 304C can represent the secondarychannels 120. In this example, each branch 304A-304C couples to a singleblood substrate layer 104 of FIG. 1A. Generally, the network of channels300 would not need to be used for the filtrate inlet manifold 114, thefiltrate substrate layer 106, or the filtrate outlet manifold 116because filtrate is not a shear sensitive fluid. In someimplementations, in which the blood inlet manifold 110 includes a trunkchannel and branch channels similar to the trunk 302 and branch channels304A-304C, the branch channels couple to the primary channel of a bloodsubstrate layer. The primary channels of the blood substrate layers thenbranches into secondary and tertiary channels.

In one implementation, a volume of fluid enters the trunk 302 at itswidest point. As the fluid travels along the trunk 302, a portion of thefluid is redirected through the branch channels 304A-304C. Although onlythree branch channels 304A-304C are shown in FIG. 3, it should beappreciated that the network of channels 300 is illustrative only, andthat the trunk 302 may be coupled to any number of the branch channels304. In some implementations, the trunk 302 couples to additional branchchannels (not shown in FIG. 3) on other sides of the trunk 302. Suchadditional channels can branch off the trunk 302 on the same side oropposite side of the trunk 302 as the branch channels 304A-304C.

The channels are configured such that the volume of fluid redirectedinto a single branch channel 304 (other than the last branch channel,i.e. branch channel 304C) is significantly less than the total volume offluid flowing through the trunk 302 at the point at which the branch 304meets the trunk 302. For example, as fluid enters the widest portion ofthe trunk 302 and travels along the trunk 302, a relatively smallpercentage of the fluid is redirected into the first branch channel304A. In various implementations, the percentage of fluid diverted intothe branch channel 304A is less than 50%, less than 40%, less than 30%,less than 20%, or less than 10% of the total fluid at the junction. Alarger percentage of the fluid continues to flow through the trunk 302and is then redirected into the branch channels 304B-304C. Thepercentage redirected is a function of the number of branch channels andis controlled by varying the dimensions of each branch channel.

These flow characteristics are achieved by selecting hydraulic diametersfor the branch channels 304A-304C that are significantly smaller thanthe hydraulic diameter of the trunk 302. The hydraulic diameters of thebranch channels 304A-304C may not necessarily be equal. In one example,the hydraulic diameters of the trunk 302 and the branch channels304A-304C are selected according to Murray's Law. Murray's Law providesa technique for selecting the radius of channels in a network in orderto balance the energy required to circulate fluid (e.g. blood) and theenergy required to metabolically support the fluid. Generally, Murray'sLaw indicates that for a primary channel having a radius of r_(p) andbranch channels having radii of r_(b1), r_(b2), etc., the relationshipbetween the radii of all of the channels should be:

r _(p) ³ =r _(b1) ³ +r _(b2) ³ + . . . +r _(bn) ³.

Murray's Law can also be used to select the relationships between thehydraulic diameters of a primary channel and branch channels in anetwork with non-circular cross sections. For example, for a primarychannel having a hydraulic diameter d_(p) and branch channels havinghydraulic diameters of d_(b1), d_(b2), etc., Murray's Law indicates thatthe relationship between the hydraulic diameters of all of the channelsshould be:

$\left( \frac{{dp}\; 1}{2} \right)^{3} = {\left( \frac{{db}\; 1}{2} \right)^{3} + \left( \frac{{db}\; 2}{2} \right)^{3} + \ldots + \left( \frac{dbn}{2} \right)^{3}}$

In some implementations, and as shown in FIG. 3, the diameter of thetrunk 302 is varied along its length to adhere to Murray's Law. Thevariation of the diameter is smooth, giving the trunk 302 a taperedshape in the direction of fluid flow. In some implementations, the angle306 formed by the centerline of the trunk 304 (i.e., the direction offluid flow through the trunk 304) and the tapered wall of the trunk 304is less than about 45°. In some implementations, the angle 306 is lessthan about 30°. In some implementations, the angle 306 is less thanabout 20°. Other walls of the trunk may also be tapered (e.g., the trunkmay have a tapered height instead of, or in addition to, a taperedwidth).

The branch channels 304A-304C are coupled to the trunk 302 and are usedto carry fluid in a direction away from the trunk 302. In someimplementations, the branch channels 304A-304C are straight channels. Inother implementations, the branch channels 304A-304C curve away from thetrunk 302, as shown in FIG. 3. Curvature of the branch channels304A-304C allows for smoother fluid flow and helps to maintain wallshear rate within an acceptable range. The radius of curvature 308 ofthe branch channels 304A-304C also affects the shear rate of fluidflowing through the network of channels 300. The network of channels 300is configured such that the radius of curvature 308 of each branchchannel 304A-304C is no less than the hydraulic diameter of thecorresponding branch channel 304A-304C.

The network of channels 300 also includes bifurcations, as illustratedby bifurcation channels 310A-310F. A bifurcation channel directs fluidflow from a first channel (e.g., branch channel 304A) into one of twoadditional channels (e.g. bifurcation channels 310A and 310B). Thebifurcation channels 310A-310F are configured to substantially evenlysplit the fluid flow from the channels to which they are coupled. Forexample, branch channel 304A and bifurcation channels 310A and 310B areconfigured such that the fluid flow rate through bifurcation channel310A is substantially the same as the fluid flow rate throughbifurcation channel 310B, and the total fluid flow rate throughbifurcation channels 310A and 310B is the same as the fluid flow ratethrough branch channel 304A. In some implementations, the bifurcationchannels are designed in accordance with Murray's Law. For example, thecube of the radius of branch channel 304A can be selected to equal thesum of the cubes of the radii of bifurcation channels 310A and 310B.

A flow divider 314, formed by the junction of the trunk 302 and thebranch 304A, has a rounded surface, as shown in FIG. 3. The roundedsurface of the flow divider 314 helps to maintain smooth fluid flowthrough the trunk 302 and the branch channel 304A. In someimplementations, the radius of curvature of the flow divider 314 is nogreater than the hydraulic diameter of the portion of the trunk 302proximate to the flow divider. The flow divider feature is describedfurther below in connection with FIG. 4.

The network of channels 300 can contain any number of bifurcations. Insome implementations, there are multiple bifurcations in a single paththrough the network of channels 300. For example, the fluid flow throughthe branch channel 304A bifurcates into bifurcation channels 310A and310B, and then further bifurcates into the bifurcation channels310C-310F. Fluid flow can also be recombined after a bifurcation, asshown in a bifurcation subnetwork 312 depicted at the top of FIG. 3.

The features described above, such as the taper of the trunk 302, thecurvature of the branches 304A-304C, and the bifurcation channels310A-310F, are selected to maintain a wall shear rate within a specifiedrange substantially throughout the entire channel network 300. In adevice that will be used to transport blood, such as the microfluidicdevice 100 of FIG. 1A or the blood substrate layer 200 of FIG. 2, thefeatures of the channel network 300 can be selected to maintain a wallshear rate in the range of about 200⁻¹-2000⁻¹. In other implementations,the channel network 300 can be designed to allow for shear rate rangesoutside of this range. Additional features that can be used to maintainblood health are further described below in connection with FIG. 4 andFIG. 5.

The selection of features described above in connection with FIG. 3 foruse in a microfluidic device can be optimized for various applications.For example, the bifurcation channels 310A-F are useful for maintainingwall shear rate and smooth fluid flow, but multiple bifurcations willoccupy a relatively large volume of space, requiring a large overalldevice size. Coupling a bifurcation network, such as the bifurcationchannels 310A-310F, to a trunk and branch network, such as the trunk 302and the branch channels 304A-304C, results in a smaller overall devicewhile preserving wall shear rates within an acceptable range throughout.

The direction of fluid flow in the examples described above isillustrative only. For example, the channel network 300 could be used totransport fluid first through the bifurcation channels 310A-310F, theninto the branch channel 304A, and finally into the trunk 302. Further,the features depicted in FIG. 3 and described above may apply to anytype of channel in the channel network 300. For example, although FIG. 3shows a taper only along the trunk 302, any other channel in the network300 can also be tapered. Similarly, the curved structure shown on thebranch channels 304A-304C could be applied to any other channel in thenetwork 300, such as the trunk 302 or the bifurcations 310A-310F.

FIG. 4 depicts a bifurcation network of channels 400 for dividing andrecombining fluid flow, similar to the bifurcation subnetwork 312 ofFIG. 3. The bifurcation network 400 includes an inlet channel 402,bifurcation channels 404A-404B, and an outlet channel 406. Thebifurcation network 400 also includes a flow divider 408 for dividingthe fluid flow from the inlet channel 402 into the bifurcation channels404A-404B, and a convergence point 410 for recombining the fluid flowfrom the bifurcation channels 404A-404B into the outlet channel 406.

The flow divider 408 is formed by the junction of the walls of thebifurcation channels 404A-404B. Fluid traveling through the inletchannel 402 is redirected into either the bifurcation channel 404A orthe bifurcation channel 404B by the flow divider 408. The flow divider408 and the bifurcation channels 404A-404B are configured tosubstantially evenly divide the total fluid flow from the inlet channel402 into the bifurcation channels 404A and 404B. In someimplementations, the walls of the bifurcation channels 404A and 404Bjoin at a sharp point, such that the radius of curvature 412 of the flowdivider 408 is effectively zero. In other implementations, the flowdivider 408 has a rounded surface connecting to the walls of thebifurcation channels 404A and 404B to allow fluid to flow more uniformlyinto the bifurcation channels 404A-404B. In some implementations, theflow divider 408 is designed with a radius of curvature 412 that is nogreater than the hydraulic diameter of the inlet channel 402. This helpsto maintain even flow and keeps the shear rate within a specified rangefor a shear sensitive fluid, such as blood.

Fluid flow through the bifurcation channels 404A and 404B is recombinedinto the outlet channel 406 at the convergence point 410, defined by thedownstream junction of the walls of the bifurcation channels 404A and404B. In some implementations, the bifurcation channels 404A and 404Beach have substantially straight walls at the convergence point 410. Inother implementations, the bifurcation channels 404A and 404B are curvedat the convergence point 410. For example, the bifurcation channels 404Aand 404B shown in FIG. 4 have opposing curvatures at the convergencepoint 410. Like the curved flow divider 408, opposing curvatures at theconvergence point 410 reduce eddie currents and vortices and maintainshear rate within a specified range, which promotes blood health whenthe channels are used in an medical device.

FIG. 5 depicts a network of channels 500 for transporting fluid. Thenetwork 500 includes a trunk channel 502 and branch channels 504A-C. Thebranch channels 504A and 504B include low pressure zones 506A and 506B,respectively. In one implementation, the network 500 represents thenetwork of channels within the blood substrate layer 200 shown in FIG.2. For example, the trunk 502 of FIG. 5 corresponds to the primarychannel 202 of FIG. 2, and the branch channels 504A-504C correspond tothe secondary channels 204 of FIG. 2. The network of channels 500 canalso represent the channels in the manifolds 110, 112, 114, and 116 andbilayers 102 of FIG. 1A. For example, the trunk 502 can represent theprimary channel 118 and the branches 504A-504C can represent thesecondary channels 120 of the blood inlet manifold 110.

In one implementation, a volume of fluid enters the trunk 502 at itswidest point. The fluid travels along the trunk 502 and is redirectedthrough the branch channels 504A-504C. Low pressure zones 506A and 506Bfacilitate redirection of fluid from the trunk 502 into the branchchannels 504A and 504B. The low pressure zones 506A and 506B are locatedat the junction of the trunk 502 and the branch channels 504A and 504B.Low fluid pressure is created by increasing the diameter of the branchchannels 504A and 504B at the junction point relative to the diameter ofthe downstream portion of the branch channels 504A and 504B. Fluidflowing through the trunk is more easily redirected into the branchchannels 504A and 504B due to the low pressure zones 506A and 506B. Asdepicted in FIG. 5, the low pressure zones 506A and 506B have a roundedshape.

The angle of the junction between the branch channels 504A-504C and thetrunk 502 is selected to allow for smooth flow of fluid from the trunk502 into the branch channels 504A-C. As shown in the FIG. 5, the angle508 formed by the junction of the branch channel 504A and the trunk 502,and measured proximate to the junction, is acute. In someimplementations, the network of channels 500 is designed so that theangle 508 measures less than about 60°. A smaller value for angle 508allows fluid flow to avoid turning at a sharp angle as fluid isredirected from the trunk 502 into the branch channel 504A. Such aconfiguration helps to maintain the wall shear rate within a specifiedrange, which can be useful if the fluid is shear sensitive (e.g.,blood).

FIG. 6 is a schematic view of a network of channels 600. The network ofchannels 600 can be useful in applications requiring the transport ofshear-sensitive fluids, such as the device shown in FIGS. 1A and 1B.Features of the channels within the network 600 can be configured tomaintain relatively low wall shear rates while occupying only a smallvolume of space. The network of channels 600 includes a primary channel602, secondary channels 604A and 604B, tertiary channels 606A-606F, andquaternary channels such as channels 608A and 608B.

The network of channels 600 can be formed within a substrate 610. In oneimplementation, the network of channels 600 can be used within the bloodsubstrate layer 104 shown in FIG. 1.

A volume of fluid enters the primary channel 602 at its widest point.The fluid is then divided between secondary channel 604A and secondarychannel 604B. In some implementations, the channels are configured suchthat the volume of fluid flowing through the secondary channel 604A issubstantially equal to the volume of fluid flowing through channel 604B.The junction of the primary channel 602 and secondary channels 604A and604B can include features similar to the features described above inconnection with the bifurcation of channel 402 into channels 404A and404B, as shown in FIG. 4. For example, the junction of primary channel602 and secondary channels 604A and 604B can include a flow divider 612for dividing fluid between secondary channels 604A and 604B as it flowsout of primary channel 602. In some implementations, the flow divider612 can have a radius of curvature that is less than or equal of thehydraulic diameter of the primary channel 602. For example, the flowdivider can form a sharp point, effectively having zero radius, as shownin FIG. 6. In other implementations, the flow divider 612 can have asmooth rounded shape formed by the junction of the walls of secondarychannels 604A and 604B. This design can help to maintain wall shear ratewithin a specified range and can help to evenly divide the fluid exitingprimary channel 602 between the secondary channels 604A and 604B.

As the fluid travels along the secondary channels 604A and 604B, aportion of the fluid is redirected through each of the tertiary channels606A-606C. The volume of fluid flowing through each tertiary channel 606can be substantially less than the total volume of fluid flowing throughthe secondary channel 604 to which the tertiary channels 606 arecoupled. For example, the tertiary channels 606A-606C can be configuredto receive equal portions of the volume of fluid flowing throughsecondary channel 604A. In some implementations, the junction of thetertiary channels 606 with the secondary channel 604 can include a flowdivider with characteristics similar to flow divider 612.

Although only three tertiary channels 606A-606C are shown connecting tothe secondary channel 604A in FIG. 6, it should be appreciated that thenetwork of channels 600 is illustrative only, and that the secondarychannels 604A and 604B may be coupled to any number of tertiary channels606. In some implementations, the secondary channels 604A and 604Bcouple to additional tertiary channels (not shown in FIG. 6) on othersides of the secondary channels 606A and 606B. Such additional channelscan branch off the secondary channels 604 on the same side or oppositeside of the secondary channels 604 as the tertiary channels 606A-606F.

In some implementations, the network of channels 600 can includefeatures described above in connection with FIG. 3. For example, eachsecondary channel 604A and 604B can direct fluid along a curved path toreduce the wall shear rate experienced by the fluid. In someimplementations, the radius of curvature of the channels 604A and 604Bcan be selected to be greater than or equal to the hydraulic diametersof the channels 604A and 604B. Other channels within the network 600 canalso have a curved shape.

In some implementations, the hydraulic diameter of the channels in thenetwork 600 can be selected according to Murray's Law. The hydraulicdiameters of the channels forming the network 600 can have a taperedshape for maintaining Murray's Law, for example by decreasing indiameter at regions of the channels where relatively less fluid ispresent.

The channels within the network 600 can branch or bifurcate into otherchannels. For example, as shown by the bifurcation of tertiary channel606C into quaternary channels 608A and 608B. The bifurcation can beformed by a flow divider having characteristics similar to those of flowdivider 612. In some implementations, the quaternary channels 608 canrecombine at a convergence point, such as convergence point 614. Asshown in FIG. 6, the quaternary channels 608A and 608B can each havesubstantially straight walls at the convergence point 614. In otherimplementations, the quaternary channels 608A and 608B are curved at theconvergence point 410. For example, the quaternary channels 608A and608B can have opposing curvatures at the convergence point 614, asdescribed above in connection with convergence point 410 of FIG. 4. Theconvergence point 614 can be designed to maintain smooth fluid flow andlow wall shear rates, which promotes blood health when the channels areused in an medical device.

The dotted lines extending from channels in the network 600 are intendedto indicate that the channels may continue on and include other channelfeatures not shown (e.g. additional channel bifurcations orrecombinations). The substrate 610 can also be extended so that thenetwork of channels 600 is fully enclosed by the substrate 610, as shownby the dotted lines extending from the edges of the substrate 610. Insome implementations, the network of channels 600 can include an outletchannel through which fluid can exit the substrate 610.

Having now described some illustrative implementations, it is apparentthat the foregoing is illustrative and not limiting, having beenpresented by way of example. In particular, although many of theexamples presented herein involve specific combinations of method actsor system elements, those acts and those elements may be combined inother ways to accomplish the same objectives. Acts, elements andfeatures discussed only in connection with one implementation are notintended to be excluded from a similar role in other implementations.

The systems and methods described herein may be embodied in otherspecific forms without departing from the characteristics thereof. Theforegoing implementations are illustrative rather than limiting of thedescribed systems and methods. Scope of the systems and methodsdescribed herein is thus indicated by the appended claims, rather thanthe foregoing description, and changes that come within the meaning andrange of equivalency of the claims are embraced therein.

What is claimed is:
 1. A microfluidic device comprising: a first networkof channels having a plurality of First Channels, each First Channelhaving a height in the range of about 50 microns to about 500 microns, awidth in the range of about 50 microns to about 1.5 millimeters, and alength in the range of about 3 centimeters to about 20 centimeters; asecond network of channels having at least one Second Channelcomplementary to one or more of the First Channels; a filtrationmembrane separating the one or more First Channels from the at least oneSecond Channel; wherein the plurality of First Channels furthercomprises: an input channel forming a primary channel, a plurality ofsecondary channels, and an outlet channel, wherein the primary channelbifurcates into first and second secondary channels at a first junction,such that a fluid flow rate through the first secondary channel issubstantially the same as a fluid flow rate through the second secondarychannel, and the total fluid flow rate between the first and secondsecondary channels is substantially the same as the fluid flow ratethrough the primary channel; a first tertiary channel connecting to thefirst secondary channel at a second junction located at a first distancealong the first secondary channel; and a second tertiary channelconnecting to the first secondary channel at a third junction located ata second distance, greater than the first distance, along the firstsecondary channel, wherein the first secondary channel and the first andsecond tertiary channels are configured such that flow of fluid throughthe first secondary channel beyond the second junction is substantiallygreater than flow of fluid into the first secondary channel.
 2. Themicrofluidic device of claim 1, wherein the plurality of First Channelsis located within a first substrate.
 3. The microfluidic device of claim2, wherein the first substrate has a thickness of no less than 50microns and no greater than 10 millimeters.
 4. The microfluidic deviceof claim 1, wherein the filtration membrane separates only a subset ofthe plurality of First Channels from the at least one Second Channel. 5.The microfluidic device of claim 1, wherein at least one of the firstand second tertiary channels bifurcates into first and second quaternarychannels at a fourth junction, such that a fluid flow rate through thefirst quaternary channel is substantially the same as a fluid flow ratethrough the second quaternary channel, and the total fluid flow ratethrough the first and second quaternary channels is substantially thesame as the fluid flow rate through the portion of the at least onetertiary channel between the first secondary channel and the fourthjunction.
 6. The microfluidic device of claim 5, further comprising aflow divider for dividing fluid flow between the first and secondquaternary channels, wherein the flow divider has a curved surfaceconnecting to the walls of the first and second quaternary channels, andthe radius of curvature of the flow divider is not greater than thehydraulic diameter of the at least one tertiary channel.
 7. Themicrofluidic device of claim 5, further comprising third and fourthquaternary channels that converge at a point where they have opposingcurvatures to form a third tertiary channel, such that all of the fluidflowing through the third and fourth quaternary channels is subsequentlytransported into the third tertiary channel.
 8. The microfluidic deviceof claim 1, wherein the diameter of at least one tertiary channel at aportion adjacent to its junction with the secondary channel issignificantly greater than the diameter of the downstream portion of theat least one tertiary channel, such that a zone of low fluid pressure iscreated at the junction.
 9. The microfluidic device of claim 1, whereinan angle formed by a centerline of at least one tertiary channel and adownstream portion of the centerline of the secondary channel to whichthe at least one tertiary channel connects measures between one andsixty degrees.
 10. The microfluidic device of claim 1, wherein theplurality of First Channels is further configured to maintain a shearrate of no less than two hundred inverse seconds and no more than twothousand inverse seconds when blood is transported through the channels.11. The microfluidic device of claim 1, wherein the walls of the primarychannel are disposed at an angle of no greater than thirty degrees withrespect to the direction of fluid flow through the primary channel. 12.The microfluidic device of claim 1, wherein at least one tertiarychannel includes a curved portion directing flow away from at least onesecondary channel.
 13. The microfluidic device of claim 12, wherein thecurved portion of the at least one tertiary channel has a radius ofcurvature that is not less than its hydraulic diameter.
 14. Themicrofluidic device of claim 1, wherein at least one of the plurality ofFirst Channels or the at least one Second Channel has a substantiallysemicircular cross section.
 15. The microfluidic device of claim 1,wherein at least one of the plurality of First Channels or the at leastone Second Channel has substantially flat top and bottom walls joined bycurved sidewalls.